The Twin Bikes System for artificial gravity in space

Exposure to microgravity (microgravity < or = 10(-4) g), beside affecting the neurovestibular and respiratory systems, greatly alters the dynamics of the circulation and leads to bone demineralization and muscle atrophy (Grigoriev and Egorov, 1991; Nicogossian, 1989a). When taken together, circulatory deconditioning and muscle atrophy lead to a reduced exercise capacity and tolerance. It is generally believed that the above modifications are completely reversible upon reentry to normal 1 g conditions, even if it is still a matter of debate whether this is really the case after very long space flights. In any case, appropriate countermeasures appear necessary for long term space flights (Nicogossian, 1989b). These countermeasures are generally based on: i) exercise training programmes, ii) appropriate suits maintaining the lower part of the body at a pressure below cabin level, thus partially reversing the headward fluid shift and iii) elastic cords pulling the subject's body towards the floor of the cabin to simulate Earth gravity. In addition, iv) artificial gravity obtained by rotation of the spacecraft, or parts thereof, was proposed since the beginning of the space era to prevent cardiovascular deconditioning and bone and muscle loss. This paper describes the Twin Bikes System and studies testing its usefulness as a tool for maintaining astronauts' physical fitness during microgravity.     

Daily 4-h head-up tilt is effective in preventing muscle but not bone atrophy due to simulated microgravity

To assess the potential value of intermittent artificial gravity as an efficient countermeasure, our previous studies have showed that daily 4-h standing (STD) is sufficient in counteracting muscle atrophy but not bone atrophy induced by simulated microgravity. The aim of the present study was to determine whether intermittent gravitational loading by daily 2-h or 4-h, +45 degrees head-up tilt (HUT) is more effective than STD in counteracting muscle and, particularly, bone atrophy due to simulated microgravity. Sprague-Dawley male rats weighing 290-300 g were subjected to a 28-d tail-suspension to simulate microgravity deconditioning. Daily HUT for 2, or 4 h was used to provide intermittent gravitational loading in foot-ward and tail-ward directions. The results showed that 4 h/d HUT was sufficient, and 2 h/d was less effective, in preventing adverse changes in muscle weights, fiber types, and cross-sectional areas (CSA) of muscles due to a 28-d simulated microgravity. The % protections by 4 h/d HUT in maintaining the CSAs of type I fibers in soleus, medial and lateral gastrocnemius and extensor digitorum longus muscles were 103%, 82%, 102%, and 83%, respectively. However, according to changes in physical and mechanical properties of femur, daily 4-h HUT was ineffective in attenuating the adverse changes in bone due to a 28-d simulated microgravity. Reductions in wet, dry, and ash weights and decreases in mechanical strength of femur did not show significant improvement by daily 2-h or 4-h HUT. Taken together, the findings indicate that the countermeasure effectiveness of daily 2-h or 4-h HUT for muscles is comparable with that by daily STD with the same durations. Daily 4-h HUT, as 4-h STD, is also ineffective in attenuating adverse changes in bone mass, but seems partially effective in preventing declines in mechanical properties due to simulated microgravity.     

Is HSP70 upregulation crucial for cellular proliferative response in simulated microgravity?

Astronauts are susceptible to a variety of conditions such as motion sickness, muscular atrophy, bone demineralization and cardiovascular deconditioning. These findings suggest that the adaptation to the absence of gravity is due, at least in part, to the effects exerted by microgravity at the cellular level. Indeed, a number of studies have indicated that gravity affects mammalian cell growth and differentiation through the modulation of gene expression. We have characterized the behaviour of endothelial cells and of the human monocytic cell line U937 cultured in the NASA-developed bioreactor to simulate microgravity, the Rotating Wall Vessels (RWV). In simulated microgravity endothelial cells showed a different behavior which was dependent from the species and from the district of origin, while U937 in the RWV proliferated slower than the controls. All the effects we observed were promptly reversible upon return to normal culture conditions. It is noteworthy that all the cells which maintained the capability to proliferate in microgravity upregulated the stress protein HSP70. We therefore propose that only the cells which sense microgravity as a stressful condition and, consequently, overexpress HSP70 maintain their proliferative potential in simulated microgravity.     

Human cardiovascular response to sympathomimetic agents during head-down bed rest: the effect of dietary sodium

Changes in sympathoadrenal function and cardiovascular deconditioning have long been recognized as a feature of the physiological adaptation to microgravity. The deconditioning process, coupled with altered hydration status, is thought to significantly contribute to orthostatic intolerance upon return to Earth gravity. The cardiovascular response to stimulation by sympathomimetic agents before, during, and after exposure to simulated microgravity was determined in healthy volunteers equilibrated on normal or high sodium diets in order to further the understanding of the deconditioning process.     

Microgravity and aging of animals

A study of changed gravity effects upon viability, life span and aging is of interest, on one hand, from a practical viewpoint in relation to the growing duration of space missions and on other hand, from a theoretical viewpoint, because gravity is one of the key factors in the evolutionary process on the Earth. In 1978 special conference titled "Space Gerontology" was held. Well known experts in space biology and physiology of aging participated in it. However, all the materiales presented at the conference were based on analogies and on what could be during exposure to microgravity rather than on real data. I shall try to discuss this problem, basing on the results of rats experiments on board "Cosmos" biosatellites and ground based model experiments. Male wistar rats examined after 1-3 weeks exposure to microgravity on board biosatellites demonstrated some changes similar to the signs [correction of sings] of aging, such as decreased motor activity, thymus involution, muscle atrophy, osteoporosis etc. But all these changes were reversible and in rats examined 3 weeks after return to the Earth we did not find any deviations from the controls.     

Effect of space flight and head-down bedrest on neuroendocrine response to metabolic stress in physically trained subjects

The aim of this study was to evaluate the association of plasma epinephrine (EPI) and norepinephrine (NE) responses to insulin induced hypoglycemia (ITT) 3 weeks before the space flight (SF), on the 5th day of SF, on the 2nd and 16th days after the landing in the first Slovak astronaut, and before and on the 5th day of prolonged subsequent head-down (-6 degrees) bed rest (BR) in 15 military aircraft pilots. Blood samples during the test were collected via cannula inserted into cubital vein, centrifuged in the special appliance Plasma-03, frozen in Kryogem-03, and at the end of the 8-day space flight transferred to Earth in special container for hormonal analysis. Insulin hypoglycemia was induced by i.v. administration of 0.1 IU/kg BW insulin (Actrapid HM) in bolus. Insulin administration led to a comparable hypoglycemia in pre-flight, in-flight conditions and before and after bed rest. ITT led to a pronounced increase in EPI levels and moderate increase in NE in pre-flight studies. However, an evidently reduced EPI response was found after insulin administration during SF and during BR. Thus, during the real microgravity in SF and simulated microgravity in BR, insulin-induced hypoglycemia activates the adrenomedullary system to less extent than at conditions of the Earth gravitation. Post-flight changes in EPI and NE levels did not significantly differ from those of pre-flight since SF was relatively short (8 days) and the readaptation to Earth gravitation was fast. It seems, that an increased blood flow in brain might be responsible for the reduced EPI response to insulin. Responses to ITT in physically fit subjects indicate the stimulus specificity of deconditioning effect of 5 days bed rest on stress response. Thus, the data indicate that catecholamine responses to ITT are reduced after exposure to real as well as simulated microgravity.     

Artificial gravity in space and in medical research

The history of manned space flight has repeatedly documented the fact that prolonged sojourn in space causes physiological deconditioning. Physiological deterioration has raised a legitimate concern about man's ability to adequately perform in the course of long missions and even the possibility of leading to circumstances threatening survival. One of the possible countermeasures of physiological deconditioning, theoretically more complete than others presently used since it affects all bodily systems, is artificial gravity. Space stations and spacecrafts can be equipped with artificial gravity, but is artificial gravity necessary? The term "necessary" must be qualified because a meaningful answer to the question depends entirely on further defining the purpose of space travel. If man intends to stay only temporarily in space, then he must keep himself in good physical condition so as to be able to return to earth or to land on any other planetary surface without undue exposure to major physiological problems resulting from transition through variable gravitational fields. Such a situation makes artificial gravity highly desirable, although perhaps not absolutely necessary in the case of relative short exposure to microgravity, but certainly necessary in interplanetary flight and planetary landings. If the intent is to remain indefinitely in space, to colonize space, then artificial gravity may not be necessary, but in this case the consequences of long term effects of adaptation to weightlessness will have to be weighed against the biological evolutionary outcomes that are to be expected. At the moment, plans for establishing permanent colonies in space seem still remote. More likely, the initial phase of exploration of the uncharted solar system will take place through successive, scope limited, research ventures ending with return to earth. This will require man to be ready to operate in gravitational fields of variable intensity. Equipping spacecrafts or space stations with some means of artificial gravity in this initial phase is, therefore, necessary without question. In a strict sense artificial gravity is conceived as a means of replacing natural gravity in space by the centripetal acceleration generated by some sort of rotating device. Rotating devices create an inertial force which has effects on bodies similar to those caused by terrestrial gravity, but artificial gravity by a rotation device is not the same as terrestrial gravity, as we shall see. Present research in artificial gravity for space exploration is projected in two main directions: artificial gravity for whole space stations and artificial gravity produced by short arm centrifuges designed for human use in space.     

Responses of neuromuscular systems under gravity or microgravity environment.

Hindlimb suspension of rats induces induces fiber atrophy and type shift of muscle fibers. In contrast, there is no change in the cell size or oxidative enzyme activity of spinal motoneurons innervating muscle fibers. Growth-related increases in the cell size of muscle fibers and their spinal motoneurons are inhibited by hindlimb suspension. Exposure to microgravity induces atrophy of fibers (especially slow-twitch fibers) and shift of fibers from slow- to fast-twitch type in skeletal muscles (especially slow, anti-gravity muscles). In addition, a decrease in the oxidative enzyme activity of spinal motoneurons innervating slow-twitch fibers and of sensory neurons in the dorsal root ganglion is observed following exposure to microgravity. It is concluded that neuromuscular activities are important for maintaining metabolism and function of neuromuscular systems at an early postnatal development and that gravity effects both efferent and afferent neural pathways.     

The theoretical limits to the power output of a muscle-tendon complex with inertial and gravitational loads

When a muscle delivers power to an inertial load through a spring, the peak power can exceed the maximum that the muscle alone could produce. Using normalized differential equations relating dimensionless quantities we show, by solving the equations either analytically or numerically, that one dimensionless constant (Xi), representing the inertial load, is sufficient to specify the behaviour during shortening of a muscle-tendon complex with linear force-velocity and force-extension properties. In the presence of gravity, an additional constant (Gamma), representing the gravitational acceleration, is required. Nonlinear force-velocity and force-extension relationships each introduce an additional constant, representing their curvature. In the absence of gravity the power output delivered to an inertial load is limited to approximately 1.4 times the maximum power of the muscle alone, and when gravity is present the power delivered is limited to approximately twice the power of muscle alone. These limits are found for the purely inertial load at Xi ca. 1 and with gravity acting at XiGamma = 0.5 with Xi arbitrarily small. The effects of nonlinear muscle and tendon properties tend to cancel each other out and do not produce large deviations from these optima. A lever system of constant ratio between muscle and load does not alter these limits. Cams and catches are required to exceed these limits and attain the high power outputs sometimes observed during explosive animal movement.     

Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity.

This study was designed to compare the effectiveness of daily short-duration -Gx gravity exposure in preventing adverse changes in skeletal and cardiac muscles and bone due to simulated microgravity. Tail suspension for 28 days was used to simulate microgravity-induced deconditioning effects. Daily standing (STD) at 1 G for 1, 2, or 4 h/day or centrifugation (CEN) at 1.5 or 2.6 G for 1 h/day was used to provide -Gx gravitation as a countermeasure. The results indicate that the minimum gravity exposure requirements vary greatly in different systems. Cardiac muscle is most responsive to such treatment: 1 h/day of -Gx gravitation by STD was sufficient to prevent adverse changes in myocardial contractility; bone is most resistant: 4 h/day of -Gx gravitation only partially alleviated the adverse changes in physical and mechanical properties of the femur. The responsiveness of skeletal muscle is moderate: 4 h/day of -Gx gravitation prevented mass reduction and histomorphometric changes in the soleus muscle during a 28-day simulation period. Increasing gravitational intensity to 2.6 G showed less benefit or no additional benefit in preventing adverse changes in muscle and bone. The present work suggests that system specificity in responsiveness to intermittent gravity exposure should be considered one of the prerequisites in proposing intermittent artificial gravity as a potential countermeasure.     

The microgravity environment for experiments on the International Space Station

Experiments are sent to space laboratories in order to take advantage of the low-gravity environment. However, it is crucial to appreciate the distinction between the real microgravity environment and "weightlessness" or "simulated microgravity". The microgravity in space laboratories may be of much smaller magnitude than the gravitational acceleration on earth. However, it is not zero, nor even one microg (defined as 1e-6 earth gravity). Moreover, the orientation is not uniaxial, as on earth. The net acceleration that acts on a space experiment arises from, e.g., orbital mechanics, atmospheric drag, and thruster firings, and it can act on the experiments in gravity-like ways. In essence, a well-defined, stable 1 g acceleration on the earth's surface is substituted for a complex array of dynamically changing accelerations with ever-changing frequency content, magnitude and direction. This paper will show measured accelerations on the Shuttle from launch to orbit, as well as the latest measurements on the International Space Station (ISS). The ISS data presented here represent over 34,790 hours of data obtained from June 2002 to April 2003 during Increments 5 and 6 of the ISS construction cycle. The quasisteady acceleration level on the ISS has been measured to be on the order of a few microg during time allotted to microgravity mode. The vibratory acceleration environment spans a rich spectrum from 0.01-300 Hz.     

Intermittent acceleration as a countermeasure to soleus muscle atrophy.

The centrifuge proposed for the Space Station will most likely be used, in part, for countermeasure studies. At present, there is a paucity of information concerning the duration and frequency of acceleration necessary to counteract the atrophy process associated with microgravity. The present study was designed to investigate intermittent acceleration during non-weight bearing of the soleus muscle and its resultant effects on muscular atrophy. Each day rats were removed from hindlimbs suspension and accelerated to 1.2 g for four 15-min periods evenly spaced over a 12-h interval. The soleus muscle experienced non-weight bearing the remaining 23 h each day. This paradigm, when repeated for 7 days, did not completely maintain the mass of soleus muscle, which was 84% of control. Interestingly, the identical protocol utilizing ground support in lieu of acceleration successfully maintained the soleus muscle mass. The failure of the centrifugation protocol to adequately maintain soleus muscle mass might be due to an undefined stress placed on the animals inherent in centrifugation itself. This stress may also explain the transient decline in food intake of the intermittent acceleration group on the 2nd and 3rd days of treatment. Also, these data support the concept that the frequency of exposure, as opposed to the duration of exposure, to weight bearing during hindlimb unweighting seems to be the more important determinant of maintaining postural muscle mass.     

Diameter changes of muscle fiber types of the inferior oblique muscle of the rabbit following denervation]

Changes in fibre diameters of extraocular muscles of the rabbit were studied at different times after denervation. The whole inferior oblique muscle hypertrophied, while some of the muscle fibres hypertrophied and others showed atrophy, depending on the fibre type. Fibre types have been determined by their histochemical enzyme profile. In the central layer of the muscle the phasic muscle fibres, which are rich in mitochondria, exhibited a transient hypertrophy being maximal 4-5 weeks after denervation and afterwards they atrophied; other phasic muscle fibres, which are poor in mitochondria, atrophied without having shown any sign of hypertrophy. Special, putatively slow tonic muscle fibres, which have low enzyme activities, underwent small long-lasting increases of their diameters. In the superficial layer of extraocular muscle there are two types of extremely thin muscle fibres rich in mitochondira. Both these fibre types hypertrophied to the greatest degree and for a very long time. Comparable changes in fibre diameters as described here for the muscle fibre types of an extraocular muscle are known from special muscle fibres in other vertebrate     

Quantitative electron-microscopy analysis of cranial nerves III, IV, and VI and of the extrinsic eye muscles in fog.

A comparative study of the quantitative data of the frog extraocular muscles and the cranial nerves that innervate them was performed. Oculorotatory muscles contain muscle fibres of at least 4 types which are arranged in heterogeneous layers. The zonal arrangement of the muscles does not occur on the cross-sections in the vicinity of muscle insertions. In these regions only two muscle fibre types are present and the total number of fibres is smaller by 70% than in the central region of the muscle. Most numerous are muscle fibres in the rectus inferior muscle, while the smallest number of fibres is found in rectus interior muscle. Three distinct types of nerve fibres are distinguished according to the following criteria: occurrence and thickness of myelin sheath, fibre diameter and ratio "g". The fibres with thin myelin sheaths indicate small diameters (1-5--6- mum) and their ratio "g" equals 0-82 +/- 0-08. They constitute about 30% of the myelinated fibres in the nerve supply of the oculorotatory muscles and about 14% in the supply of the retractor bulbi muscle. Both the value of the ratio "g" and a greater number of these fibres in the nerve supply of the muscles that contain slow contracting muscle fibres indicate that they are rather slow conducting nerve fibres. The range of the diameters of the fibres with thick myelin sheaths is greater (3-5--13-5 mum) and their "g" equals 0-66 +/- 0-06. These fibres constitute about 70% of the myelinated ones in the nerve supply of the oculorotatory muscles and 86% in the supply of the retractor bulbi muscles. The value of the ratio "g" in these fibres indicates that they are fast contracting ones. The smallest diameters are found in the myelinated fibres (0-5--1-7 mum). These fibres occur frequently in all the examined nerves; they constitute 36--47% of the total number of all the nerve fibres. The frog extraocular muscles are characterized by an abundal nerve supply which is reflected in the low innervation ratio (1:4--1:5). On the distal cross-section of nerves the number of nerve fibres is greater than on the proximal ones. Ganglionic neurons occur sporadically around the nerves; in the nerve III synaptic contacts between two neurons were observed.     

失重状态下肌萎缩研究进展

失重条件下人和动物生理状态会发生一系列的变化,其中骨骼肌萎缩和力量下降较为显著,目前其发生的机制仍不明确且缺少特效的干预措施。本文从肌肉湿重及肌纤维横截面积的变化、肌纤维类型的变化、肌纤维超微结构的变化、肌梭的适应性变化四个方面进行简要阐述,探讨肌肉萎缩的可能发生机制。     

Arrest of developmental conversion of type II to type I fibres after suspension hypokinesia

Summary The effects of hypokinesia and of the lack of gravity on muscle fibres, fibre type composition and myosin light chain pattern, as well as on muscle mechanoreceptors were investigated in the slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles of young growing and adult rats after suspension hypokinesia (SH) of their hind limbs. The animals were suspended by their tail so that their hind limbs were relieved of their normal weight-bearing function for 3–6 weeks.In normal 3-to 4-week-old rats the SOL contained about 50% type I fibres and their percentage increased up to about 80% until the 10th week, with simultaneous reduction of type IIA fibres. After 3 to 6 weeks of suspension treatment maintained from 3-to, 4-week-old rats up to 6 to 10 weeks of age, the SOL still only contained about 50% of type I fibres. The content of fast LC₁ and LC₂ in the SOL of 6-week-old rats after 3 weeks of suspension was higher than that of control litter-mates reflecting the higher occurrence of IIA fibres in the suspended solei. No changes in fibre type composition were observed after SH performed in adult rats.SH thus leads, in young animals, to the arrest of conversion of type IIA to type I fibres resulting in the persistence of the fibre type composition and of the myosin light chain pattern corresponding to those present in the SOL at the time of the onset of suspension. In both young and adult rats, SH markedly decreased the mass and the mean cross-sectional area of the SOL, mainly due to the severe atrophy of type I fibres. We observed no signs indicating conversion of type I back to type IIA muscle fibres due to the SH either in young or adult animals.In contrast to profound changes in the SOL, no significant differences were found in the EDL in any of the parameters studied.No changes in the investigated parameters of muscle spindles and tendon organs were observed after SH, performed either in young or in adult rats.We thus conclude that SH leads to muscle atrophy and that it influences mainly or exclusively type I fibres in muscles with a postural function such as the SOL. It is suggested that in young rats SH arrests changes in the SOL motoneurones, which remain unable to ensure the normal developmental transformation of type IIA into type I fibres, thus preventing conversion of the SOL into a typical slow-twitch muscle.     

Passive stretch inhibits central corelike lesion formation in the soleus muscles of hindlimb-suspended unloaded rats.

Hindlimb suspension unloading (HSU) is a ground-based model simulating the effects of microgravity unloading on the musculoskeletal system. In this model, gravity causes the hind foot of the rat to drop, opening the front of the ankle to 90-105 degrees plantar flexion at rest. As HSU proceeds, the normal weight-bearing angle of 30 degrees dorsiflexion is achieved progressively less, and the contraction range of soleus is abbreviated. Our laboratory reported that 12 days of HSU caused central corelike lesions (CCLs) of myofibril breakdown (Riley DA, Slocum GR, Bain JL, Sedlak FR, Sowa TE, and Mellender JW. J Appl Physiol. 69: 58-66, 1990). The present study investigated whether daily stretch of the calf muscles prevents CCL formation. The soleus muscles of HSU Sprague-Dawley male rats (approximately 287 g) were lengthened by unilateral ankle splinting at 30 degrees. Compared with the nonsplinted side, splinting for 10 or 20 min per day in awake rats significantly decreased CCLs in soleus by 88 and 91%, respectively (P < 0.01). Compared with control muscle wet weight, 20-min splinting reduced atrophy by 33%, whereas 10-min splinting ameliorated atrophy by 17% (P < 0.01). Bilateral soleus electromyograph recording revealed higher levels of contractile activity on the splinted side during splinting. To isolate the effects of stretch from isometric contractile activity, contractions were eliminated by whole animal anesthesia with isoflurane during 10-min daily splinting. The percentage of fibers with CCLs was reduced by 57%, and the average lesion size was 29% smaller in the stretched muscle (P < 0.05). Soleus muscle wet weight and fiber area were unaltered by stretch alone. Loaded contractions during splinting are necessary to prevent muscle fiber atrophy. Passive muscle stretch acts to maintain myofibril structural integrity.     

Default network connectivity decodes brain states with simulated microgravity

With great progress of space navigation technology, it becomes possible to travel beyond Earth’s gravity. So far, it remains unclear whether the human brain can function normally within an environment of microgravity and confinement. Particularly, it is a challenge to figure out some neuroimaging-based markers for rapid screening diagnosis of disrupted brain function in microgravity environment. In this study, a 7-day ?6° head down tilt bed rest experiment was used to simulate the microgravity, and twenty healthy male participants underwent resting-state functional magnetic resonance imaging scans at baseline and after the simulated microgravity experiment. We used a multivariate pattern analysis approach to distinguish the brain states with simulated microgravity from normal gravity based on the functional connectivity within the default network, resulting in an accuracy of no less than 85 % via cross-validation. Moreover, most discriminative functional connections were mainly located between the limbic system and cortical areas and were enhanced after simulated microgravity, implying a self-adaption or compensatory enhancement to fulfill the need of complex demand in spatial navigation and motor control functions in microgravity environment. Overall, the findings suggest that the brain states in microgravity are likely different from those in normal gravity and that brain connectome could act as a biomarker to indicate the brain state in microgravity.     

Cytoplasmic streaming inChara rhizoids

Summary In-vivo videomicroscopy ofChara rhizoids under 10^–4g demonstrated that gravity affected the velocities of cytoplasmic streaming. Both, the acropetal and basipetal streaming velocities increased on the change to microgravity. The endogenous difference in the velocities of the oppositely directed cytoplasmic streams was maintained under microgravity, yet the difference was diminished as the basipetal streaming velocity increased more than the acropetal streaming velocity. Direction and structure of microfilaments labeled by rhodamine-phalloidin had not changed after 6 min of microgravity.Abbreviations g gravitational acceleration - Nizemi slow rotating centrifuge microscope - Texus technological experiments under reduced gravity